Amid continuing concerns about the health risks from testosterone replacement drugs, such as Androgel and Testim, new prescription guidelines call for doctors to ensure that men who have a confirmed diagnosis of hypogonadism, and to avoid prescribing the drugs to men with prostate cancer, breast cancer, pre-existing heart problems or who plan to have children in the near future.

The Endocrine Society published its clinical practice guidelines for the evaluation and treatment of male hypogonadism late last week in the Journal of the American Medical Association (JAMA), which are designed to instruct doctors on best practices in testing men for chronically low testosterone and whether they should be treated using testosterone drugs.

In recent years, television advertisements and other drug marketing has encouraged men to speak with their doctor about the use of low testosterone treatments if they experience symptoms like decreases in energy, strength, sex drive or other problems that are also linked to natural drops in testosterone levels as all men age. However, as a number of studies have highlighted the risk of heart attacks, strokes, blood clots and death that maybe caused by side effects of testosterone therapy, health experts have suggested that the medications have been widely over-prescribed to many men who have no real medical need for the treatments.

Testosterone replacement therapy, which includes blockbuster drugs like Androgel, Testim, Axiron and others, were initially expected to be a niche treatment for men suffering from testosterone deficiency caused by a medical condition, known as hypogonadism. However, as men receive prescription of the drugs for life-style reasons, the industry grew to generate more than $2 billion in sales annually in recent years.

“The effects of testosterone on energy, physical performance, mood, and cardiometabolic factors continue to be explored, but in general, the treatment of hypogonadal younger men often improves symptoms related to testosterone deficiency. In contrast, testosterone treatment for middle-aged and older men with functional decline, even for those with clearly low serum testosterone levels, offers modest and inconsistent benefit,” the guidelines note. “Despite such uncertainties, ‘low T’ clinics and intensive direct-to-consumer advertising have contributed to a substantial recent increase in testosterone prescribing.”

The new guidelines lay out when hypogonadism can be established; calling for two or more measurements to be taken. The guidelines say hypogonadism should be tested for in men who may have abnormal sex hormone levels, such as those suffering from obesity, diabetes, nephrotic syndrome, hypothyroidism, acromegaly, and in those taking steroids or progestins. It also calls for testing of older patients, those suffering from HIV, cirrhosis, hepatits, hyperthyroidism and in men taking estrogen or anticonvulsant medications.

However, the guidelines call for much stringent use of the drugs in practice, indicating that they should only recommended for men who have diagnosed cases of hypogonadism.

The Endocrine Society does not recommend testosterone use in men who plan on having children in the near future, or who have breast or prostate cancer, who have suffered a heart attack or stroke within the last six months, or men with prostate problems, untreated obstructive sleep apnea, severe lower urinary tract infections, uncontrolled heart failure or thrombophilia.

The guidelines also call for doctors to only offer men over the age of 65 testosterone after they have been diagnosed for hypogonadism, and after they have had an individualized discussion about the risks and benefits.

The group also calls for medical monitoring several times during the first year and on an annual basis after that.

According to allegations raised in the testosterone prescription litigation, pharmaceutical companies marketing the drugs withheld important safety warnings from consumers and the medical community, while promoting the widespread use of the medications among men without a true need for testosterone treatments.

Given the similar allegations raised in the lawsuits, more than 6,500 cases filed throughout the federal court system have been consolidated for pretrial proceedings as part of a multidistrict litigation (MDL), which is centralized before U.S. District Judge Matthew Kennelly in the Northern District of Illinois.

While two global testosterone settlements involving Axiron and Testim claims are expected to resolve about one-third of the pending litigation, no agreements have been reported involving Androgel cases brought against AbbVie for injuries associated with their market-leading testosterone gel product.

AbbVie has already been hit with several massive jury awards in early bellwether trials, including $150 million in punitive damages in July 2017 and a verdict of $140 million in a second case in October 2017. However, the award in the first case was overturned during post-trial motions, and retrial is set for this month.